During the past 15 years, the DERC, with its Core Laboratories, Enrichment Program and support for Pilot and Feasibility studies, has played a major role in allowing the expansion in the scope and intensity of research at the Joslin Diabetes Center and Harvard Medical School. The DERC has provided essential support for interdisciplinary studies and junior faculty, and a critical infrastructure for both basic and clinical research. It is not surprising, therefore, that over this period there has been a further evolution and strengthening of the research effort at the Joslin. Recognizing this growth in research activity and the importance of the research mission, the Joslin added additional research space by renovating space previously used for administrative functions. This has resulted in improved laboratory space for individual investigators and the DERC Core Laboratories. In this renewal application, we have attempted to build on our strengths by eliminating Core Laboratories that were underutilized (the Peptide Biochemistry Core), adding new Cores (Flow Cytometry) and restructuring existing Cores including the Advanced Microscopy Core, Radioligand Assay Core (now the Specialized Assay Core), the Genetics Core and the Animal Resources Core (now the Mouse Physiology Core). The Pilot and Feasibility grant program has been expanded to provide larger grants to four scientists and the invitations to compete for these awards have been extended to scientists outside Joslin affiliated with Harvard institutions in the Longwood Area (e.g., Harvard Medical School, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Children's Hospital, Dana Farber Cancer Institute, Center for Blood Research). Within the DERC and the Joslin, we have been particularly encouraged over the past five years by the development of the younger faculty who have been supported directly and indirectly by the DERC, such as Drs. Myers, Sharma, Patti, Doria, Stanton and others. These individuals, along with more established investigators, and new recruited faculty including Drs. Christophe Benoist and Diane Mathis, create the scientific base and strength of the DERC. Finally, the strong intellectual stimulus provided by the activities of the Enrichment Program has a major impact, not only at the Joslin, but also in the Harvard-Longwood Medical Area.